Hematopoiesis News Volume 8.34 | Aug 29 2017

TOP STORY

Hematopoietic Stem Cell Involvement in BCR–ABL1-Positive ALL as Potential Mechanism of Resistance to Blinatumomab Therapy

Researchers provide evidence that CD19-negative relapse after CD19-directed therapy in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) may be due to selection of preexisting CD19-negative malignant progenitor cells. They present two BCR–ABL1-fusion-positive BCP-ALL patients with CD19-negative myeloid lineage relapse after blinatumomab therapy and showed BCR–ABL1-positivity in their HSC/progenitor/myeloid compartments at initial diagnosis by fluorescence in situ hybridization after cell sorting. [Blood] Abstract

(Ranked by impact factor of the journal)

Mice Expressing Kras^G12D in Hematopoietic Multipotent Progenitor Cells Develop Neonatal Myeloid Leukemia

Investigators developed a model of juvenile myelomonocytic leukemia using mice that express Kras^G12D in multipotent progenitor cells. Mutant mice had altered hematopoietic stem and progenitor cell populations in the BM and spleen that were hypersensitive to granulocyte macrophage–CSF due to hyperactive RAS/ERK signaling. [J Clin Invest] Full Article

Secreted Protein Del-1 Regulates Myelopoiesis in the Hematopoietic Stem Cell Niche

The authors identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, they found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular cells, and cells of the osteoblastic lineage. [J Clin Invest] Full Article

Modulation of Occluding Junctions Alters the Hematopoietic Niche to Trigger Immune Activation

Scientists showed that bacterial infection induces the cellular immune response by modulating occluding-junctions at the hematopoietic niche. Occluding-junctions formed a permeability barrier that regulated the accessibility of prohemocytes to niche derived signals. [eLife] Full Article

Low Oxidative Stress-Mediated Proliferation via JNK-FOXO3a-Catalase Signaling in Transplanted Adult Stem Cells Promotes Wound Tissue Regeneration

The authors elucidate the mechanistic role of catalase at 10µM H₂O₂-induced proliferation of mouse bone marrow stromal (BMSC) and hematopoietic stem/progenitor (HSPC) cells. BMSCs and HSPCs depicted an increased growth rate and colony formation, in presence of 10µM but not 100µM concentration of H₂O₂, an effect that was perturbed by vitamin C. [Antioxid Redox Signal] Abstract

Dermatopontin in Bone Marrow Extracellular Matrix Regulates Adherence but Is Dispensable for Murine Hematopoietic Cell Maintenance

Researchers explored marrow extracellular matrix (ECM) using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. They found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. [Stem Cell Reports] Full Article

CCCTC-Binding Factor Is Essential to the Maintenance and Quiescence of Hematopoietic Stem Cells in Mice

Using a tamoxifen-inducible CCCTC-binding factor (CTCF) conditional knockout mouse system, scientists determined whether CTCF regulates the homeostatic maintenance of HSCs. In adult mice, acute systemic CTCF ablation led to severe bone marrow failure and the rapid shrinkage of multiple c-Kit^hi progenitor populations, including Sca-1⁺ HSCs. [Exp Mol Med] Full Article

CLINICAL RESEARCH

Phase I Clinical Trial Using mbIL21 Ex–Vivo Expanded Donor-Derived NK Cells after Haploidentical Transplantation

To test the hypothesis that NK cells can decrease the risk of leukemia relapse, researchers initiated a Phase-I dose-escalation study of expanded donor NK cells infused before and after haploidentical hematopoietic stem cell transplantation for high-risk myeloid malignancies. The goals were to determine the safety, feasibility and maximum tolerated dose. [Blood] Abstract

Phase I Dose Escalation Multicenter Trial of Pracinostat Alone and in Combination with Azacitidine in Patients with Advanced Hematologic Malignancies

Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, investigators conducted a Phase I study to assess the safety, maximum tolerated dose, recommended Phase II dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies. [Cancer] Abstract

Efforts to Enhance Blood Stem Cell Engraftment: Recent Insights from Zebrafish Hematopoiesis

Recent studies in zebrafish have revealed novel genes that are required for HSC induction and niche regulation of HSC homeostasis. Manipulation of these signaling pathways and cell types may improve HSC bioengineering, which could significantly advance critical, lifesaving HSCT therapies. [J Exp Med] Full Article

Osteopontin and Their Roles in Hematological Malignancies: Splice Variants on the New Avenues

The authors summarize total osteopontin (tOPN) roles in hematological malignancies (HMs) and provide evidence that OPN-splicing isoforms can also modulate specific functions in HMs biology. They summarize that upregulated tOPN can modulate HMs progression, inducing cell adhesion, invasion, angiogenesis, cell differentiation and extramedullary and/or central nervous system infiltration. [Cancer Lett] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoiesis research field.

Physicians’ Education Resource^® to Host Three Satellite Symposia

Physicians’ Education Resource^® will conduct three CME-Accredited Satellite Symposia. The programs will focus on some of the most pressing issues in hematology. [Press release from Physicians’ Education Resource^® (Business Wire Inc.) discussing research to be presented at the American Society of Hematology (ASH)’s 59^th Annual Meeting & Exposition, Atlanta] Press Release

Jazz Pharmaceuticals and ImmunoGen, Inc. Announce a Strategic Collaboration and Option Agreement to Develop and Commercialize Antibody-Drug Conjugate Products

Jazz Pharmaceuticals plc and ImmunoGen, Inc. announced that the companies have entered into a collaboration and option agreement granting Jazz Pharmaceuticals exclusive, worldwide rights to opt into development and commercialization of two early-stage, hematology-related antibody-drug conjugate programs, as well as an additional program to be designated during the term of the agreement. [Jazz Pharmaceuticals plc] Press Release

CSL Behring to Acquire Biotech Company Calimmune and Its Proprietary Stem Cell Gene Therapy Platform

CSL Behring announced that it has agreed to acquire Calimmune, Inc., a biotechnology company focused on the development of ex vivo HSC gene therapy with R&D facilities in Pasadena, California and Sydney, Australia for an upfront payment of $91 million. [CSL Behring (PR Newswire Association LLC.)] Press Release

Stem Cell Agency Invests in Clinical Trial that Uses a One-Two Punch to Confuse and Kill Leukemia Cells

The California Institute for Regenerative Medicine Board is investing $18.29 million in a clinical trial being run by Thomas Kipps, M.D., Ph.D., of the University of California, San Diego. He is using a combination strategy to kill the cancer stem cells that help chronic lymphocytic leukemia – and other cancers – survive traditional therapies, such as chemotherapy, and cause a relapse. [California Institute for Regenerative Medicine] Press Release

New Ambitious Research Program Receives DKK 100 Million for Research into Leukemia and New Treatment

Professor Kristian Helin heads a new research program, which has received DKK 100 million from the Novo Nordisk Foundation. The program, which falls under DanStem, is clinically focused and aims to develop and test new forms of treatment for leukemia. [University of Copenhagen] Press Release

U.S. FDA and European Medicines Agency Accept Regulatory Submissions for BOSULIF^® (Bosutinib) for the Treatment of Patients with Newly Diagnosed Ph⁺ Chronic Myeloid Leukemia

Pfizer Inc. and Avillion LLP announced that a supplemental New Drug Application (sNDA) for BOSULIF^® has been accepted for filing and granted Priority Review by the FDA. If approved, the sNDA would expand the approved use of BOSULIF to include patients with newly diagnosed chronic phase Philadelphia chromosome-positive (Ph⁺) chronic myeloid leukemia. [Pfizer Inc.] Press Release

Moleculin Announces Filing with FDA of IND for Its Leukemia Drug Annamycin

Moleculin Biotech, Inc. announced it has filed with the FDA an Investigational New Drug (IND) application to study annamycin in the treatment of relapsed or refractory acute myeloid leukemia (AML). [Moleculin Biotech, Inc.] Press Release

Unum Therapeutics Announces Active Investigational New Drug (IND) Application for ACTR087 in Combination with SEA-BCMA in Patients with Relapsed/Refractory Multiple Myeloma

Unum Therapeutics Inc. announced that an IND application is now active for ACTR087 T cells in combination with a novel antibody, SEA-BCMA, for the treatment of adult patients with relapsed/refractory multiple myeloma. [Unum Therapeutics Inc.] Press Release

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

In the last few days alone, the FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

FDA Warns US Stem Cell Clinic of Significant Deviations

The FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

NEW AACR-NCI-EORTC International Conference on Molecular Targets & Cancer Therapeutics
November 5-9, 2017
Philadelphia, Pennsylvania, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Hematopoietic Stem Cells and Malignancies (Albert Einstein College of Medicine)

NEW Scientist – Regulators of Hematopoiesis (Università di Roma)

Postdoctoral Scholar – Hematopoiesis and Leukemia (Penn State College of Medicine)

Director – Allogeneic Hematopoietic Stem Cell Transplantation (Princess Margaret Cancer Centre)

Postdoctoral Research Fellow – Metabolic Diseases & Hematological Malignancies (Columbia University)

Postdoctoral Fellow – Epigenetics and Immune Signaling in Cancer (Thomas Jefferson University)

Postdoctoral Fellow – Regenerative Medicine (Loma Linda University)

Associate Director, Clinical Development – Hematology/Oncology (Jazz Pharmaceuticals)

Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance)

Postdoctoral Fellow – Age Associated Changes of the Hematopoietic Stem Cell Compartment (National Institutes of Health/National Institute on Aging)

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